Chronic immune and chronic inflammatory diseases (CICIDs) are a group of severe and debilitating diseases that include Multiple Sclerosis (MS), Chronic Fatigue Syndrome (CFS) and Rheumatoid Arthritis (RA) amongst others.
CICIDs are often pleomorphic in their presentation, the severity of symptoms depending on the extent of the disease.
CICIDs can be highly debilitating. Chronic inflammation can lead to the disruption of normal immune functions (through the cleavage of RNase L protein for example). RNase L protein cleavage and decreased levels of RNase L inhibitor (RLI) mRNA have been linked with chronic immune diseases such as MS and CFS.
RNase L is the terminal enzyme in the 2-5A synthetase/RNase L antiviral pathway (for review, see Bastide et al, 2002, in: Chronic Fatigue Syndrome, a Biological Approach, CRC Press, Boca Raton Fla., 2002, pp. 1-15). RNase L (as homodimer) is able to degrade viral RNA (to stop the infectious process) and cellular RNA (to cause the removal of the damaged cell by a process known as programmed cell suicide or apoptosis).
RNase L protein fragments may have enzymatic activity but are unregulated as these protein fragments lack the regulatory (i.e., dimeric) sequences that the native enzyme possesses. A dysfunctional immune system cannot respond correctly to further challenges, completing a vicious circle leading to chronic impairment of the immune defense system. In such cases, chronic infections and chronic inflammation may be the result.
The utility of RNase L protein fragments (such as the 37-kDa fragment) as clinical markers for CFS and MS is well documented (see e.g. De Meirleir et al, 2000, AM. J. Med. 108:99-105). Tests based on these markers are, however, technically complex.